The goal of this project is to understand the underlying physiological mechanisms of different involuntary movement disorders. The tools we use include clinical neurophysiological methods such as electroencephalography, electromyography, and transcranial magnetic stimulation and neuroimaging with positron emission tomography and functional magnetic resonance imaging. Currently active projects in the Section include studies of tremor, tic, and periodic movements in sleep. We are using physiological methods to see if criteria can be defined to make the diagnosis of psychogenic tremor. One test that looks promising is measuring the frequency spectrum of the tremor in one extremity while asking the patient to make movements with specified frequencies in the opposite extremity. We are also collecting information regarding patterns of muscle recruitment, sensory modulation and cortical activity (using EEG) associated with psychogenic movements. Analysis reveals that the preparatory cortical activity (measured by pre-movement potentials) is similar to that preceding voluntary movements. The pattern of stimulus-response was found to be highly variable and inconsistent in patients who had stimulus sensitive myoclonus. We have shown that somatosensory evoked potentials are a sensitive measure of disease burden in all type 3 neuronopathic Gaucher disease (GD3) patients. The mean potential amplitude in patients differed significantly from controls and from type 1 Gaucher patients. Amplitude and the IQ of patients also was significantly correlated. Somatosensory evoked potentials were also evaluated in patients with restless legs syndrome. The study was done to test the hypothesis that excitability of the sensory system is increased in these patients. Compared to controls, a significant increase in the amplitude of the posterior tibial nerve somatosensory evoked potential was seen in patients. Preliminary analysis of parkinsonian tremor showed coherence between the motor cortex and muscle at the tremor frequency. In contrast, cortico-muscular coherence at the tremor frequency was not observed at the tremor frequency in normal (physiologic tremor) and essential tremor patients. These findings suggest an important role of the motor cortex in parkinsonian tremor. In the future, this method might be a useful tool to the early stage of Parkinson?s disease from other disorders. We treated a patient with Lafora Body Disease with a ketogenic diet attempting to control his epilepsy. Additionally his myoclonus and mental state have improved. Concomitantly, significant insulin resistance and marked hyperinsulinemia despite ketosis was noticed, a new finding in Lafora disease which suggests a possible role of Laforin (a novel tyrosine phosphatase) in insulin signaling.